Abstract
The crucial event in the development of transmissible spongiform encephalopathies (TSEs) is the conformational change of a host-encoded membrane protein - the cellular PrPC - into a disease associated, fibril-forming isoform PrPSc. This conformational transition from the α8-helix-rich cellular form into the mainly β- sheet containing counterpart initiates an autocatalytic reaction which leads to the accumulation of amyloid fibrils in the central nervous system (CNS) and to neurodegeneration, a hallmark of TSEs. The exact molecular mechanisms which lead to the conformational change are still unknown. It also remains to be brought to light how a polypeptide chain can adopt at least two stable conformations. This review focuses on structural aspects of the prion protein with regard to protein-protein interactions and the initiation of prion protein misfolding. It therefore highlights parts of the protein which might play a notable role in the conformational transition from PrPC to PrPSc and consequently in inducing a fatal chain reaction of protein misfolding. Furthermore, features of different proteins, which are able to adopt insoluble fibrillar states under certain circumstances, are compared to PrP in an attempt to understand the unique characteristics of prion diseases.
Keywords: Transmissible spongiform encephalopathy, prion protein, structural propensities, misfolding
Current Molecular Medicine
Title: Prion Protein Misfolding
Volume: 9 Issue: 7
Author(s): L. Kupfer, W. Hinrichs and M. H. Groschup
Affiliation:
Keywords: Transmissible spongiform encephalopathy, prion protein, structural propensities, misfolding
Abstract: The crucial event in the development of transmissible spongiform encephalopathies (TSEs) is the conformational change of a host-encoded membrane protein - the cellular PrPC - into a disease associated, fibril-forming isoform PrPSc. This conformational transition from the α8-helix-rich cellular form into the mainly β- sheet containing counterpart initiates an autocatalytic reaction which leads to the accumulation of amyloid fibrils in the central nervous system (CNS) and to neurodegeneration, a hallmark of TSEs. The exact molecular mechanisms which lead to the conformational change are still unknown. It also remains to be brought to light how a polypeptide chain can adopt at least two stable conformations. This review focuses on structural aspects of the prion protein with regard to protein-protein interactions and the initiation of prion protein misfolding. It therefore highlights parts of the protein which might play a notable role in the conformational transition from PrPC to PrPSc and consequently in inducing a fatal chain reaction of protein misfolding. Furthermore, features of different proteins, which are able to adopt insoluble fibrillar states under certain circumstances, are compared to PrP in an attempt to understand the unique characteristics of prion diseases.
Export Options
About this article
Cite this article as:
Kupfer L., Hinrichs W. and Groschup H. M., Prion Protein Misfolding, Current Molecular Medicine 2009; 9 (7) . https://dx.doi.org/10.2174/156652409789105543
DOI https://dx.doi.org/10.2174/156652409789105543 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Vascular, Oxidative, and Synaptosomal Abnormalities During Aging and the Progression of Type 2 Diabetes
Current Neurovascular Research Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies
Current Drug Targets Serum Insulin Degrading Enzyme Level and Other Factors in Type 2 Diabetic Patients with Mild Cognitive Impairment
Current Alzheimer Research Vascular Changes of the Retina and Choroid in Systemic Lupus Erythematosus: Pathology and Pathogenesis
Current Neurovascular Research Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways
Current Pharmaceutical Design Biological Basis of Ageing, Age-related Diseases and Interventions
Current Pharmacogenomics and Personalized Medicine Identification of Electrophysiological Changes in Alzheimer's Disease: A Microarray Based Transcriptomics and Molecular Pathway Analysis Study
CNS & Neurological Disorders - Drug Targets Thrombolytic Treatment of Cardiac Myxoma-Induced Ischemic Stroke: A Review
Current Drug Safety A Model on the Induction of Adverse Vascular Long-Term Effects of NSAIDs
Medicinal Chemistry Natural Animal Models of Neurodegenerative Protein Misfolding Diseases
Current Pharmaceutical Design Central Hemodynamics in Risk Assessment Strategies: Additive Value Over and Above Brachial Blood Pressure
Current Pharmaceutical Design Treatment Approaches in Elderly Patients with Head and Neck Cancer
Anti-Cancer Agents in Medicinal Chemistry Determinants of Paraoxonase 1 Status: Genes, Drugs and Nutrition
Current Medicinal Chemistry The Effects of Obesity on the Cerebral Vasculature
Current Vascular Pharmacology Editorial [Hot Topic: Cognition Therapeutics (Guest Editor: Miao-Kun Sun)]
Current Drug Targets - CNS & Neurological Disorders Complications Associated with Recombinant Tissue Plasminogen Activator Therapy for Acute Ischaemic Stroke
CNS & Neurological Disorders - Drug Targets Treatment of Catatonia with Asenapine in a Patient with Schizotypal Personality Disorder, Psychotic Depression and Septic Shock from SARSCoV- 2 - A Case Report
CNS & Neurological Disorders - Drug Targets On the Interaction of β-Amyloid Peptides and α7-Nicotinic Acetylcholine Receptors in Alzheimer’s Disease
Current Alzheimer Research Nanotechnology Based Delivery Systems of Drugs Currently Used to Treat Alzheimer’s Disease
Nanoscience & Nanotechnology-Asia Polyphenols: A Diverse Class of Multi-Target Anti-HIV-1 Agents
Current Drug Metabolism